17874-76-9

The general procedure for the synthesis of 6-(methoxycarbonyl)nicotinic acid from methanol and 2,5-dipyridinecarboxylic acid is as follows: with reference to the literature method 66, a selective esterification reaction was first carried out on 2,5-pyridinedicarboxylic acid (58). 58 was dissolved in methanol, a catalytic amount of sulfuric acid was added and the reaction was refluxed for 2 hours. Upon completion of the reaction, the monomethyl ester product (59) was purified by recrystallization from water in 42% yield. Subsequently, the monomethyl ester 59 was converted to the corresponding acyl chloride (60) by reflux reaction with an excess of thionyl chloride. Finally, the acylation of compound 35 was completed using the reflux reaction of the chloride 60 with an excess of aluminum trichloride in dichloromethane (DCM) (Scheme 10).

[1] Patent: WO2011/103321, 2011, A1. Location in patent: Page/Page column 23
[2] Patent: US2006/293319, 2006, A1. Location in patent: Page/Page column 47
[3] Patent: WO2007/70173, 2007, A2. Location in patent: Page/Page column 145-146
[4] European Journal of Inorganic Chemistry, 2010, # 13, p. 1913 - 1928
[5] Patent: WO2012/121973, 2012, A1. Location in patent: Page/Page column 89